P1239: TISLELIZUMAB, A PD-1 INHIBITOR FOR RELAPSED/REFRACTORY MATURE T- AND NK-CELL NEOPLASMS: RESULTS FROM A PHASE 2 STUDY
Authors: E. Bachy, K. J. Savage, H. Huang, Y. L. Kwong, G. Gritti, Q. Zhang, A. M. Liberati, J. Cao, H. Yang, S. Hao, J. Hu, K. Zhou, F. Russo, H. Zhang, W. Sang, J. Ji, A. J. M. Ferreri, G. L. Damaj, H. Liu, W. Zhang, X. Ke, C. Ghiggi, S. Huang, X. Li, H. Yao, J. Paik, W. Novotny, W. Zhou, H. Zhu, J. Huang, P. L. Zinzani
Journal: HemaSphere (2022)

Background: Effective treatment choices for patients (pts) with relapsed/refractory (R/R) mature T- and NK-cell neoplasms after failure of standard therapies are limited. Tislelizumab (TIS), a humanized anti–PD-1 mAb, demonstrated outstanding efficacy and favorable safety in pts with R/R classical Hodgkin lymphoma or solid tumors. Aims: To evaluate the safety and efficacy of TIS in pts with R/R mature T- and NK-cell neoplasms. Methods: This was a global, multicenter, single-arm, open-label, phase 2 study (NCT03493451). Pts were enrolled into 3 cohorts stratified by the type of T- and NK-cell neoplasms to receive TIS 200 mg intravenously every 3 weeks until disease progression or intolerable toxicity. Eligible pts had ≥1 prior systemic therapy, disease progression during or after most recent therapy completion or refractory disease, Eastern Cooperative Oncology Group performance score ≤2, and life expectancy ≥6 mo. All pts gave informed consent. Primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS) in cohorts 1 and 2, and safety. Results: A total of 77 pts were treated. Cohort 1 included 22 pts with R/R extranodal NK and T-cell lymphomas; cohort 2 included 44 pts with R/R mature T-cell neoplasms (21 peripheral T-cell lymphoma not otherwise specified, 11 angioimmunoblastic T-cell lymphoma, and 12 anaplastic large cell lymphoma); and cohort 3 included 11 pts with R/R cutaneous T-cell lymphomas (CTCL; stage ≥1B; 8 mycosis fungoides and 3 Sézary syndrome). Of all pts, 76.6% had advanced-stage disease, 51.9% had refractory disease, and 49.4% had ≥3 prior systemic regimens. Median treatment cycles for cohorts 1, 2, and 3 were 5 (range 1-37), 4.5 (range 1-38), and 17 (range 3-25), respectively. Cohort 3 had promising efficacy (median study follow-up [FU] 16.6 mo); ORR 45.5%; CR 9.1%; median DOR 11.3 mo (95% CI, 2.76-11.30); median PFS 16.8 mo (95% CI, 2.60-16.82); and median OS not reached (NR) (95% CI, 4.90-not estimable [NE]). Modest efficacy was reported in cohort 1 (median study FU 8.4 mo): ORR 31.8%; CR 18.2%; median DOR NR (95% CI, 2.66-NE); median PFS 2.7 mo (95% CI, 1.45-5.32); and median OS 8.8 mo (95% CI, 3.25-NE). Modest efficacy also was noted in cohort 2 (median study FU 9.3 mo): ORR 20.5%; CR 9.1%; median DOR 8.2 mo (95% CI, 2.50-NE); median PFS 2.7 mo (95% CI, 2.56-4.76); and median OS 13.3 mo (95% CI, 7.66-26.22). Most frequent adverse events (AEs) were pyrexia (32.5%), anemia (18.2%), arthralgia (18.2%), and diarrhea (15.6%); most frequent grade ≥3 AEs were anemia (7.8%), pneumonia (6.5%), and neutropenia (5.2%). Any-grade immune-mediated AEs occurred in 22 (28.6%) pts, most frequently hypothyroidism (10.4%), hyperglycemia (5.2%), and rash (5.2%). Grade ≥3 AEs occurred in 4 (5.2%) pts and included increased blood creatine phosphokinase, hepatitis, hypothyroidism, rash, and urticaria (1 pt each). No treatment-related AEs led to death. Summary/Conclusion: TIS was well tolerated, achieving modest efficacy in R/R mature T- and NK-cell neoplasms, with some long-lasting remissions particularly in CTCL. Further studies are needed to determine the biologic features associated with response and explore optimal combination therapies.